In patients affected by Marfan Syndrome (MFS), the synthesis of extracellular matrix microfibrils is impaired by mutations in the FBN1 gene, resulting in a fragile and unstable connective tissue. Thus, the syndrome is characterized for its systemic phenotypic effects, affecting mainly the bone, ocular and cardiovascular tissues, the latter being the most worrying, responsible for life expectancy reduction due to ruptured aortic aneurysms. Alterations in fibrillin-1 synthesis, encoded by FBN1, do not only alter the arrangement of the extracellular matrix through the fragmentation of elastic fibers. The vascular cells are also affected causing vascular stiffness, especially endothelial cells, which due to their anatomical position become more vulnerable to the impacts of blood flow in a weakened tissue. The endothelium, in addition to being responsible for regulating homeostasis, acts as a comunication mediator with vascular smooth muscle cells and has an important role on immune and inflammatory responses due to its permeability. In a pathological context, these functions are impaired, creating a propitious scenario for the development of aneurysms, which can culminate in rupture of the vessel. Different models have been suggested for studying MFS and among them hiPSC (human induced pluripotent stem cells) has been shown to be an important tool for modeling the disease. In order to understand the cellular and molecular mechanisms involved on the syndrome, our lab group has generated hiPSC lineages with induced FBN1 mutations. These mutations simulate the dominat-negative expression and the haploinssuficiency, representing different ways to affect fibrilin-1 expression. Considering the relevance of the cardiovascular phenotype on MFS, this study intends to establish a standard protocol for different lineages of hiPSC derivation in endothelial cells and analyze the different patterns of fibrilin-1 expression.
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